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BACKGROUND@#T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domains (TIGIT), an inhibitory receptor expressed on T cells, plays a dysfunctional role in antiviral infection and antitumor activity. However, it is unknown whether TIGIT expression on T cells influences the immunological effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inactivated vaccines.@*METHODS@#Forty-five people living with HIV (PLWH) on antiretroviral therapy (ART) for more than two years and 31 healthy controls (HCs), all received a third dose of a SARS-CoV-2 inactivated vaccine, were enrolled in this study. The amounts, activation, proportion of cell subsets, and magnitude of the SARS-CoV-2-specific immune response of TIGIT + CD4 + and TIGIT + CD8 + T cells were investigated before the third dose but 6 months after the second vaccine dose (0W), 4 weeks (4W) and 12 weeks (12W) after the third dose.@*RESULTS@#Compared to that in HCs, the frequency of TIGIT + CD8 + T cells in the peripheral blood of PLWH increased at 12W after the third dose of the inactivated vaccine, and the immune activation of TIGIT + CD8 + T cells also increased. A decrease in the ratio of both T naïve (T N ) and central memory (T CM ) cells among TIGIT + CD8 + T cells and an increase in the ratio of the effector memory (T EM ) subpopulation were observed at 12W in PLWH. Interestingly, particularly at 12W, a higher proportion of TIGIT + CD8 + T cells expressing CD137 and CD69 simultaneously was observed in HCs than in PLWH based on the activation-induced marker assay. Compared with 0W, SARS-CoV-2-specific TIGIT + CD8 + T-cell responses in PLWH were not enhanced at 12W but were enhanced in HCs. Additionally, at all time points, the SARS-CoV-2-specific responses of TIGIT + CD8 + T cells in PLWH were significantly weaker than those of TIGIT - CD8 + T cells. However, in HCs, the difference in the SARS-CoV-2-specific responses induced between TIGIT + CD8 + T cells and TIGIT - CD8 + T cells was insignificant at 4W and 12W, except at 0W.@*CONCLUSIONS@#TIGIT expression on CD8 + T cells may hinder the T-cell immune response to a booster dose of an inactivated SARS-CoV-2 vaccine, suggesting weakened resistance to SARS-CoV-2 infection, especially in PLWH. Furthermore, TIGIT may be used as a potential target to increase the production of SARS-CoV-2-specific CD8 + T cells, thereby enhancing the effectiveness of vaccination.
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Humans , Antibodies, Viral , CD8-Positive T-Lymphocytes , COVID-19/complications , COVID-19 Vaccines/immunology , HIV Infections/complications , Receptors, Immunologic , SARS-CoV-2الملخص
BACKGROUND@#Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine can induce a potent cellular and humoral immune response to protect against SARS-CoV-2 infection. However, it was unknown whether SARS-CoV-2 vaccination can induce effective natural killer (NK) cell response in people living with human immunodeficiency virus (PLWH) and healthy individuals.@*METHODS@#Forty-seven PLWH and thirty healthy controls (HCs) inoculated with SARS-CoV-2 inactivated vaccine were enrolled from Beijing Youan Hospital in this study. The effect of SARS-CoV-2 vaccine on NK cell frequency, phenotype, and function in PLWH and HCs was evaluated by flow cytometry, and the response of NK cells to SARS-CoV-2 Omicron Spike (SARS-2-OS) protein stimulation was also evaluated.@*RESULTS@#SARS-CoV-2 vaccine inoculation elicited activation and degranulation of NK cells in PLWH, which peaked at 2 weeks and then decreased to a minimum at 12 weeks after the third dose of vaccine. However, in vitro stimulation of the corresponding peripheral blood monocular cells from PLWH with SARS-2-OS protein did not upregulate the expression of the aforementioned markers. Additionally, the frequencies of NK cells expressing the activation markers CD25 and CD69 in PLWH were significantly lower than those in HCs at 0, 4 and 12 weeks, but the percentage of CD16 + NK cells in PLWH was significantly higher than that in HCs at 2, 4 and 12 weeks after the third dose of vaccine. Interestingly, the frequency of CD16 + NK cells was significantly negatively correlated with the proportion of CD107a + NK cells in PLWH at each time point after the third dose. Similarly, this phenomenon was also observed in HCs at 0, 2, and 4 weeks after the third dose. Finally, regardless of whether NK cells were stimulated with SARS-2-OS or not, we did not observe any differences in the expression of NK cell degranulation markers between PLWH and HCs.@*CONCLUSION@#s:SARS-CoV-2 vaccine elicited activation and degranulation of NK cells, indicating that the inoculation of SARS-CoV-2 vaccine enhances NK cell immune response.
الموضوعات
Humans , COVID-19 Vaccines/therapeutic use , COVID-19 , SARS-CoV-2 , Killer Cells, Natural , HIV Infections , Antibodies, Viralالملخص
OBJECTIVE To evaluate the qualit y of Xihuang pills ，and to screen the differential markers affecting its quality . METHODS Using muskone as internal reference ，the content of α-pinene and other 4 components were determined by quantitative analysis of multi -components by single marker （QAMS），and compared with the results of external standard method . The fingerprints of 13 batches of Xihuang pills were established by gas chromatography （GC）method. Cluster analysis （CA）and orthogonal partial least squares discriminant analysis （OPLS-DA） were performed by SPSS 25.0 software and SIMCA 14.1 software. The variable importance projection （VIP）value greater than 1 was used as the standard to screen differential markers affecting the quality of the samples . RESULTS The contents of α-pinene，octyl acetate and β-elemene measured by QAMS were 0- 0.628 4，0.378 0-2.679 4 and 0.320 9-0.815 4 mg/g，respectively. The contents of α-pinene，octyl acetate ，β-elemene and musk ketone measured by external standard method were 0.001 5-0.627 1，0.378 0-2.594 7，0.329 2-0.837 0 and 0.385 7-0.806 0 mg/g， respectively. The relative error of the content determination results of the two methods was less than 4%. There were 26 common peaks in 13 batches of Xihuang pills ，and 3 common peaks ，such as octyl acetate ，β-elemene and musk ketone ，were identified ； their similarities were 0.912-0.946. 13 batches of samples could be divided into two categories （S1-S2，S6-S10，S13 were clustered into one category and S 3-S5，S11-S12 were clustered into one category ）. VIP values of peak 7，11，10，17 and 16 were all greater than 1. CONCLUSIONS The content of 4 components such as α-pinene in Xihuang pills combined with GC fingerprint and chemical pattern recognition analysis can be used to evaluate the quality of Xihuang pills . The components corresponding to 5 common peaks such as peak 7 may be differential markers affecting the quality of the samples .
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Objective@#A large phase Ⅲ comparison trial of pemetrexed to docetaxel showed similar efficacy for treating advanced non-small-cell lung cancer. In this paper, the prognostic factors for the outcome of second-line therapy with pemetrexed or docetaxel in patients with advanced non-small-cell lung cancer were retrospective analyzed. At the same time, the impact of first-line chemotherapy on the outcome of second-line chemotherapy was analyzed.@*Methods@#For 134 patients with advanced NSCLC were randomly assigned to receive pemetrexed 500 mg/m2 or docetaxel 75 mg/m2 on day 1 of a 21-day cycle. According to the type of first-line therapy, patients were divided into three groups: platinum combined with gemcitabine group (50 cases), platinum combined with taxane group (38 cases) and other therapies group (46 cases). Univariate and multivariate analysis methods were used to compute the relationship between prognostic factors, including age, gender, stage at diagnosis, performance status, best response to first-line therapy and time elapsed from first- to second-line therapy, and patients′ overall survival.@*Results@#Through multivariate analysis we found patients′ gender, stage at diagnosis, performance status and best response to first-line therapy was significant correlatedion with overall survival. Among them, median survival time for female and male patients was 9.2 and 6.8 months respectively with a significant difference between them (P<0.05). In addition, median survival time for stage Ⅲ and Ⅳ was 9.3 and 7.4 months respectively with a significant difference (P<0.05). At the same time, median survival time for ECOG PS 0, 1 and 2 was 12.1, 7.8 and 2.9 months with a significant difference (P<0.01). For complete/partial remission patients, stable condition patients, disease progression patients after first-line therapy, the median survival time was 15.4, 10.7 and 4.3 months respectively with a significant difference (P<0.01). Additional, median survival time for first-line therapy with platinum combined with gemcitabine was significant longer than that treated with platinum combined with taxane and other therapies:8.9 months vs. 6.8 months vs. 7.4 months.@*Conclusions@#Four prognostic factors including patients′ gender, performance status, stage at diagnosis and best response to first-line therapy should be considered in the second-line therapy setting with pemetrexed or docetaxel in patients with advanced non-small-cell lung cancer. This paper has potential clinical value in the second-line therapy with pemetrexed or docetaxel for patients with advanced NSCLC.
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Hedgehog (HH) signaling pathway is a classic signaling pathway which controls embryonic development.Recent studies show that HH signaling pathway plays an important role in the tumorigenesis and development of cancer.Breast cancer stem cells (BCSCs) is closely associated with malignant tumor metastasis,relapse and treatment resistance.HH pathway plays crucial roles in maintaining the characters of BCSCs,and will probably become a novel therapeutic target of breast cancers.
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As the main drug in colorectal cancer chemotherapy,oxaliplatin is gradually infiltrated into other malignancies therapy.But oxaliplatin-induced peripheral neuropathy limits its clinical application.The mechanisms of oxaliplatin neurotoxicity are not yet clear.Recent researches show that the acute neurotoxicity of oxaliplatin is mediated through changes in Na + transient conductances.And the function of the mitogen-activated protein kinases in chronic neuropathy has already been demonstrated in vitro.Furthermore,numerous indicators can be used to predict oxaliplatin-induced peripheral neuropathy,which bring the hope for improving the continuity of chemotherapy and realizing personalized medicine therapy.
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Objective To explore the relationship between operation scores and the expression of caveolin-1 ( Cav-1 ) protein in the cortex of mice.Methods Male Kunming mice were used and divided into two groups (excellent group and bad group) according to the training scores after 4 days' Y-maze learning training.The expression of cav-1 protein in cortex and hippocampus of the mice with different scores were measured through Western blot technology.Results Cav-1 protein expression of excellent group( Cav-1/β-actin was 5.71 + 1.11 ) in the cortex was significantly higher than that of the bad group ( Cav-1/β-actin was 1.69 + 0.20) (P ＜ 0.01 ).While there was no significant difference in the two groups in the expression of Cav-1 protein in hippocampus(P ＞ 0.05 ).Conclusion The operation scores have distinct correlation with the expression of Cav-1 protein in the cortex of mice.
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Objective To confirm the deviation between the present charge and real cost of nursing by comparing them between PICC and jugular veins catheter,and the advantages and disadvantages were weighed between them in tumor patients undergoing chemotherapy.Methods The cost of manpower,financial resources or materials for 106 patients with PICC,68 patients with jugular veins catheter were measured,accounted and statistically analyzed with the ladder sharing method for project cost.Comparing the cost between calculation cost and current charging standard,and the cost and clinical application was studied.Results The real cost of PICC was (2259.99±30.99)Yuan and current charging standard was 1532.79 Yuan,the deviation was -727.20 Yuan,and the real cost of jugular veins catheter was (393.86±33.93) Yuan,and current charging standard was 292.13 Yuan,the deviation was -101.73 Yuan.The complication rate was 12％ in PICC,17％ in jugular veins catheter.The real cost of nursing on PICC and jugular veins catheter was higher than current charging standard,and the real cost of single nursing on PICC was 5.74 times higher than jugular veins catheter.The cost remains unchanged with 4～6 course of chemotherapy treatments in a year.Conclusions The advantages of PICC are more than jugular veins catheter,so the preferred choice is PICC,and jugular veins catheter comes secondary.
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Objective To evaluate the clinical pathology meaning of atypical squamous cell of undetermined significance (ASCUS) in cervical cytology. Methods The clinical data of 2118 cases who underwent cervical liquid thin-prep cell test (TCT) were analyzed retrospectively, ASCUS and squamous epithelium (SIL) were diagnosed according to the classification of the data TBS cytology, the histopathological examination results were tracked. Results The incidence of ASCUS was 3.4% (72/2218), and the ratio for SIL ( 1.2%, 25/2118) was 2.9. In the cellular pathology of ASCUS, there were four aspects, atypical surface cells and atypical hollowed cells in 16 cases (22.2%), atypical atrophy of the squamous epithelial cells in 11 cases (15.3%), atypical mature or immature metaplastic cells 28 cases (38.9%), atypical cells less influence diagnosis 17 cases (23.6%). Tracking the histologic findings in 43 cases with chronic cervicitis 22 cases (51.2%), low level squamous epithelium neoplasia in 12 cases (27.9%), high levels of squamous epithelial change in 8 cases (18.6%), squamous cell carcinoma 1 case(2.3%). Conclusion ASCUS exists within the risk of squamous lesions, management should be strengthened.
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<p><b>OBJECTIVE</b>To investigate the potential developmental toxicity of Radix Ophiopogonis decoction in SD rats.</p><p><b>METHOD</b>Timed-pregnant SD rats were given Radix Ophiopogonis decoction (26.9 g x kg(-1)) or vehicle (distilled water) by gavage on gestation days 6-17. Maternal clinical sign, abortions, premature deliveries, and body weight were monitored throughout gestation. At termination (gestation days 20) pregnant females were evaluated for clinical status and gestational outcome; live fetuses were examined for gender, external, visceral and skeletal malformation and variations.</p><p><b>RESULT</b>No deaths, premature deliveries or dose-related clinical signs were attributed to Radix Ophiopogonis decoction. Maternal body weight and body weight gain were not affected. There were no effects on fetus weight and viability, incidences of fetal malformation and variation.</p><p><b>CONCLUSION</b>These results demonstrated that Radix Ophiopogonis decoction had no detectable adverse effects in either the treated F0 female rats or the fetuses.</p>
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Animals , Female , Humans , Male , Pregnancy , Rats , Body Weight , Drugs, Chinese Herbal , Embryonic Development , Fetal Development , Fetal Weight , Models, Animal , Ophiopogon , Chemistry , Random Allocation , Rats, Sprague-Dawleyالملخص
<p><b>OBJECTIVE</b>To investigate the genotoxicity of Cortex Fraxini decoction.</p><p><b>METHOD</b>Mouse lymphoma assay (MLA) and mouse bone marrow micronucleus test (MNT) were used. In MLA, four dose levels of 1.71, 3.42, 6.83 and 13.65 g (crude drug) x L(-1) were exposed with I5178Y cells for 3 hours with and without metabolic activation, then expressed for 2 days. The mutation frequency plates were prepared and incubated for 12-13 days. Colony size in each plate was scored, and the total mutation frequency and the percentage of small colony mutants were calculated. In MNT, contained three dose levels of 7.14, 14.28 and 28.55 mg (crude drug) x kg(-1) and 10 ICR mice (5 males/5 females) were in each group. The mice were given in every 24 hours by oral gavage twice and sacrificed after 24 hours of the last dosing. Both femur bones were collected to prepare the smear. For each mouse, the number of micronucleated polychromatic erythrocytes (MNPCE) in 2 000 polychromatic erythrocytes was counted, and the mean of rate of MNPCE of each group was calculated.</p><p><b>RESULT</b>In MLA, the results indicated that the total mutation frequency of four dose levels showed a dose-dependent increase, there was statistically significant difference at high concentrations compared with negative control (P < 0.01), and the percentage of small colony mutants was similar with positive control in the absence of metabolic activation. The total mutation frequency of each dose level was similar with negative control in the presence of metabolic activation. In MNT, the results indicated that the decoction did not show inhibitory action for bone marrow, and the induced rate of MNPCE of each group was not significantly increased comparing with negative control.</p><p><b>CONCLUSION</b>Cortex Fraxini decoction induces the tk(+/-) gene mutation and chromosome damage in L5178Y cells in vitro without metabolic activation, it hints that the direct mutagens may be within the test article. Cortex Fraxini decoction does not show chromosome damage of bone marrow in ICR mice, it has not genotoxicity in vitro/in vivo with metabolic activation under this study condition.</p>
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Animals , Female , Male , Mice , Cell Line, Tumor , DNA Damage , Drugs, Chinese Herbal , Toxicity , Erythrocytes , Mice, Inbred ICR , Mutagenicity Tests , Mutagens , Toxicity , Mutationالملخص
Objective To express the novel fibronectin-binding protein Fba of group A streptococcus(GAS)and analyze its immunogenicity,so that to evaluate the immune responses to GAS infection.Methods fba gene was amplified by polymerase chain reaction(PCR)and confirmed by sequencing.Then it was cloned into pGEX4T-2 vector and Fba protein was expressed in E.coli BL21.The protein expression was identified by enzyme-linked immunosorbent assay(ELISA)and Westernblot.The sera from mice infected with GAS and anti-streptolysin-O positive patients were detected using microtiter plates coated with purified Fba protein as antigen.Afterward Balb/C mice were immunized with this purified protein and the sera were collected after the third immunization for the detection of IgG titer.Results It was confirmed by ELISA and Western blot that the recombinant Fba protein had a specific affinity with anti-Fba sera of rabbit.The anti-serum IgG titer of mice imrnunized with Fba protein was up to 1:4800.Conclusions GAS infection or Fba protein immunization are able to induce high serum titer of anti-Fba which could react specifically with the recombinant Fba protein.It indicates that Fba protein has good immunogenicity and antigenicity.So Fba protein could be a GAS candidate vaccine and an important tool to detect anti-GAS titer in GAS infected patients.
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<p><b>BACKGROUND</b>Somatostatin receptor (SSTR), as a marker gene in tumors, is being valued gradually. With five subtypes have been identified, many researches are carried out to explore the amino acid sequence of SSTR family members, the molecular biological characteristics, the distribution and expression in the normal tissue and the tumor, and their specific ligands. In this study, the expression and significance of SSTR (SSTR2A, SSTR5) and epidermal growth factor receptor (EGFR) in human non-small cell lung cancer (NSCLC) were investigated, and the relationship among them were evaluated.</p><p><b>METHODS</b>The expressions of SSTR2A, SSTR5 and EGFR in 62 NSCLC tissues and 7 lung tissues adjacent to the cancer tissues were detected by immunohistochemical method (SP method). All cases were followed up.</p><p><b>RESULTS</b>In 62 cases of NSCLC, the positive rate of SSTR2A and SSTR5 expression was 48.4% (30/62) and 71.0% (44/62) respectively. The positive rate of SSTR2A and SSTR5 was closely related to TNM stage (P < 0.05), but not to other clinical characteristics of NSCLC (P > 0.05). The positive rate of EGFR expression was 56.5% (35/62), but 0 in 7 lung tissues adjacent to the cancer tissues. The positive rate of EGFR was not related to the age, sex, smoking or not, tumors histological type, tumor size, TNM stage, differentiation classification and the lymph node metastasis (P > 0.05). There was negative relation between the expression of SSTR2A, SSTR5 and EGFR in NSCLC. The 3-year survival rate of patients with SSTR2A and SSTR5 expression was 64.52% and 65.91% respectively, 45.16% and 22.22% for those without expression (P < 0.05); The 3-year survival rate of patients with EGFR expression was 30.77% and 69.44% for those without expression (P < 0.05 ).</p><p><b>CONCLUSIONS</b>The expression of SSTR and EGFR is significantly upregulated in NSCLC and a negative relation exists between their expressions. Detection of expression of SSTR2A, SSTR5 and EGFR might be helpful to evaluate lymph node metastasis, pathological stages and prognosis of NSCLC.</p>
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Objective Better drying methods of Forsythia suspense leaves was studied to provide some basis for the development and utilization of Forsythia suspense leaves. Methods A RP-HPLC method was used on XTerraTMRP8 (3.9 mm?150 mm, 5 ?m) column with acetonitrile-0.1% acetic acid solution (12 : 88) as mobile phase for forsythoside. The detection wavelength of forsythoside was at 328 nm and detection temperature was 30 ℃. Results The contents of forsythoside was higher when dry, microwave drying, absorbent paper drying, steaming 2～10 min, cooking 2～10 min was used to deal with Forsythia suspense leaves. The contents of forsythoside was lower when dried, drying, infrared drying, vacuum drying was used to deal with Forsythia suspense leaves. Conclusion Steaming 2～10 min, cooking 2～ 10 min is more appropriate for drying of Forsythia suspense leaves, when factors of the contents of forsythoside, the cost and ease of operation were considerd.
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Objective Chromatography fingerprint of Radix Codonopsis of different age from Shanxi province was studied to provide the reference for the science appraisal of intrinsic quality of Radix codonopsis. Method A RP-HPLC method was applied on GraceSmart-RP18 (250 mm?4.6 mm, 5 ?m) column with acetonitrile-0.1% acetic acid gradient elution as mobile phase, and the flow-rate was 0.6 mL/min. The detection wavelength was at 268 nm and the column temperature was at 30 ℃. Result Chromatography fingerprint of Radix Codonopsis can demonstrate obviously the difference and the similarity of Radix Codonopsis of different age. The RSD were lower than 3% in the precision, stability and the repetitiveness trial, and the codonopsis pilosula alkyne glucoside can be used as the reference to identify the active composition of Radix Codonopsis. Conclusion The method was simple, reproducible and reliable. The integrity of fingerprint can be used to supply the reference for the quality control of Radix Codonopsis from Shanxi provice.
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<p><b>BACKGROUND</b>Endostar™ (rh-endostatin, YH-16) is a new recombinant human endostatin developed by Medgenn Bioengineering Co. Ltd., Yantai, Shandong, P.R.China. Pre-clinical study indicated that YH-16 could inhibit tumor endothelial cell proliferation, angiogenesis and tumor growth. Phase I and phase II studies revealed that YH-16 was effective as single agent with good tolerance in clinical use.The current study was to compare the response rate , median ti me to progression (TTP) ,clinical benefit andsafety in patients with advanced non-small cell lung cancer ( NSCLC) , who were treated with YH-16 plus vi-norelbine and cisplatin (NP) or placebo plus NP.</p><p><b>METHODS</b>Four hundred and ninety-three histologically or cy-tologically confirmed stage IIIB and IV NSCLC patients , withlife expectancy > 3 months and ECOG perform-ance status 0-2 , were enrolledin a randomized ,double-blind ,placebo-controlled , multicenter trial ,either trialgroup : NP plus YH-16 (vinorelbine 25 mg/m² on day 1 and day 5 ,cisplatin 30mg/m² on days 2 to 4 , YH-167.5mg/m² on days 1 to 14) or control group : NP plus placebo (vinorelbine 25 mg/m² on day 1 and day 5 ,cis-platin 30 mg/m² on days 2 to 4 ,0.9% sodium-chloride 3 .75 ml on days 1 to 14) every 3 weeks for 2-6 cycles .The trial endpoints included response rate ,clinical benefit rate ,time to progression,quality of life and safety .</p><p><b>RESULTS</b>Of 486 assessable patients , overall response rate was 35.4% in trial group and 19.5% in controlgroup (P=0 .0003) . The median TTP was 6 .3 months and 3 .6 months for trial group and control group respectively (P < 0 .001) . The clinical benefit rate was 73 .3 %in trial group and 64.0% in control group (P=0 .035) .In untreated patients of trial group and control group ,the response rate was 40 .0% and 23.9%(P=0 .003) ,the clinical benefit rate was 76 .5 % and 65 .0 % (P=0 .023) ,the median TTP was 6 .6 and 3 .7months (P=0 .0000) ,respectively .In pretreated patients of trial group and control group ,the response ratewas 23.9% and 8.5%(P=0 .034) ,the clinical benefit rate was 65.2% and 61.7%(P=0 .68) ,the median TTP was 5 .7 and 3 .2 months (P=0 .0002) ,respectively . The relief rate of clinical symptoms in trial groupwas higher than that of those in control group ,but no significance existed (P > 0 .05) . The score of quality oflife in trial group was significantly higher than that in control group (P=0 .0155) after treatment . There were no significant differences in incidence of hematologic and non-hematologic toxicity , moderate and severe sideeffects betweentrial group and control group .</p><p><b>CONCLUSIONS</b>The addition of YH-16 to NP regimen results in significantly and clinically meaningful improvement in response rate , median time to tumor progression,and clinical benefit rate compared with NP alone in advanced NSCLC patients . YH-16 in combination with chemotherapy shows a synergic activity and a favorable toxic profile in advanced cancer patients .</p>
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<p><b>BACKGROUND</b>To evaluate and compare the effects and toxicity of the domestic product of recombinant mutant human tumor necrosis factor (rmhTNF) combined with chemotherapy and chemotherapy alone in the treatment of patients with non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>Two hundred patients with NSCLC in multicenter were randomly devided into trial group (150 cases) and control group (50 cases). Chemotherapy with CAP regimen was given to the patients. Meanwhile, rmhTNF injection of 4×10⁶U/m² was also given from the 1st to 7th days, the 11th to 17th days on the chemotherapy cycle in the trial group. The control patients received chemotherapy alone. Twenty-one days were as a cycle, 2 cycles were given to each patient. The chemotherapeutic effects and toxicity were observed and compared between the two groups after the therapy.</p><p><b>RESULTS</b>of the 200 patients, 5 cases in the trial group and 3 cases in the control group were out of the trial because of economy. The other 192 cases (145 cases in the trial group and 47 cases in the control group) could be analyzed and evaluated the clinical effects and toxicity. The response rate of chemotherapy was 46.90% (68/145) in the trial group and 17.02% (8/47) in the control group respectively ( P =0.001). The KPS scores was 86.02±9.74 in the trial group, and 80.14±9.10 in the control group ( P =0.025). No significant difference of degree III+IV toxicity was observed between the two groups ( P > 0.05). The side effects related to rmhTNF included slight fever, cold-like symptoms, pain and red and swelling in the injection site. All of them were mild and didn't need any treatment and disappeared after the therapy. There were no severe abnormality of liver and kidney function and ECG in both groups.</p><p><b>CONCLUSIONS</b>The results demonstrate that the effects of domestic rmhTNF combined with chemotherapy are remarkably higher than that of chemotherapy alone in the treatment of NSCLC. rmhTNF can increase the sensitivity to chemotherapy and improve the quality of life of the patients with slight toxicity. Hence rmhTNF is worth expanding clinical use.</p>
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<p><b>BACKGROUND</b>To evaluate and compare the effects and toxicity of the domestic product of nrhTNF combined with chemotherapy in the trial group and chemotherapy alone in the control group in the treatment of patients with non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>Ninety patients with NSCLC in multicenter were randomly devided into trial group and control group. Each group had 45 patients. Chemotherapy with CAP regimen was given for the patients in the trial group. Meanwhile, nrhTNF injection of 4×10⁶U/m ² was also given from the 1st to 7th days, the 11th to 17th days on the chemotherapy course. Twenty-one days were as a cycle, 2 cycles were given each patients. Chemotherapy alone with CAP regimen was given in the control group. The chemothepeutic effects and toxicity were observed and compared between the two groups after the therapy.</p><p><b>RESULTS</b>Of the 90 patients, 3 cases in each group were out of the trial because of economy. The other 84 cases (each group had 42 patients) could be used to analyze and evaluate the clinical effects and toxicity. The response rate of chemotherapy was 47.62% (20/42) in the trial group and 19.05% (8/42) in the control group (P=0.002) respectively. The KPS was 85.02±10.74 in the trial group, and 81.35±9.63 in the control group (P=0.038). No significant difference of degree III+IV toxicity was observed between the trial group and control group (P > 0.05). The side effects related to nrhTNF included slight fever, cold like symptoms, pain, and red and swelling in injection site. All of them were mild and didn't need any treatment and disappeared after the therapy.</p><p><b>CONCLUSIONS</b>The results demonstrate that the effects of domestic nrhTNF combined with chemotherapy can remarkably higher than that of chemotherapy alone in the treatment of NSCLC. It is able to increase the sensitivity to chemotherapy and improve the quality of life of the patients. The toxicity is also slight and is worth to expand clinical use, so as to further evaluate its effect and toxicity.</p>
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Objective: To evaluate the cytotoxicity and targeting ability of self-developed paclitaxel-octreotide (PTX-OCT) conjugates on A549 non-small cell lung cancer (NSCLC) cells and Calu-6 NSCLC cells. Methods: Conjugates PTX-OCT and 2PTX-OCT were synthesized by our school. Reverse transcription-polymerase chain reaction was used to detect mRNA of human somatostatin receptor subtypes (SSTRs) using specific primers. The cells were treated with different concentrations (1, 100 nmol/L and 1 ?mol/L) of paclitaxel and the conjugates for different time periods (24-72 h); we also set up a control group. MTT assay was used to evaluate the cell viability after treatment; cell cycle perturbations were determined by FAC Scan flow cytometer 24 h after treatment with 1 ?mol/L paclitaxel, PTX-OCT, and 2PTX-OCT. Results: Both A549 cell and Calu-6 cell expressed the mRNA of SSTR2 and SSTR5; no SSTR mRNA was detected in the fibroblasts. The conjugates had a similar cytotoxicity to paclitaxel; they both effectively inhibited the growth of A549 cells and Calu-6 cells in a concentration-and time-dependent manner. After 72 h treatment with 1 ?mol/L paclitaxel, PTX-OCT and 2PTX-OCT, the survival rates of A549 cells were (26.9?7.3)%, (26.6?9.2)% and (35.7?4.3)%, respectively; the survival rates of Calu-6 cells were (29.5?5.0)%, (28.2?9.7)% and (26.5?4.9)%, respectively. The survival rate A549 cells at 72 h after treatment was lower than that at 24 h after treatment(P
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0.05).There was a negative correlation between the EGFR expression with the expression of SSTR2A and SSTR5 in NSCLC tissues.The 3-year survival rates were 64.5% and 65.9% in patients positive of SSTR5 and SSTR2A,respectively;and were 45.2% and 22.2% for those negative of SSTR5 and SSTR2A,respectively(P